CYC-116

A potent and selective Aurora A/Aurora B inhibitor with IC50 of 8.0/9.2 nM; shows >50-fold selectivity over CDK1/2/4/7/9; exhibits antiproliferative activity against a broad panel of cancer cell lines with IC50<1 uM; orally bioavailable and possesses anticancer activity in mice. (In Vitro) :CYC-116 also inhibits VEGFR2, Src, Lck AND FLT3 with with Kis of 44, 82, 280, 44 nM, respectively. CYC-116 may have broad-spectrum antitumor activity. CYC-116 shows potent antiproliferative activity against cancer cell lines with with IC50s of 0.599, 0.59, 0.241, 0.34, 0.725, 1.375, 0.471, 0.034, 0.372, 0.681, 0.151, 1.626, 0.775, 0.308, 0.110, 0.09 for MCF7, HeLa, Colo205, HCT-116, HT29, K562, CCRF-CEM, MV4-11, HL60, NCI-H460, A2780, BxPC3, HuPT4, Mia-Paca-2, Saos-2, Messa cells. Treatment with 1.25 μM CYC-116 for 7 h results in complete inhibition of histone H3 phosphorylation in HeLa cell lysates. (In Vivo) :Oral administration of CYC-116 at dose levels of 75 and 100 mg/kg q.d. causes tumor growth delays of 2.3 and 5.8 days, which translates into specific growth delays of 0.32 and 0.81, respectively. The mean relative tumor volumes of mice receiving CYC-116 at both dose levels are less than those of vehicle-treated mice for the duration of the study period. At 100 mg/kg po q.d., the reduction in growth is statistically significant on days 6 and 9.